The pituitary gland is attached by a stalk to the region in the base of the brain known as the hypothalamus. The pituitary gland has two lobes, the anterior and posterior lobes. The posterior lobe of the pituitary gland stores and passes onto the general circulation two hormones manufactured in the hypothalamus, these being vasopressin and oxytocin. The anterior lobe of the pituitary gland secretes a number of hormones, which are complex protein or glyco-protein molecules that travel through the blood stream to various organs which, in turn, stimulate the secretion into the blood stream of other hormones from the peripheral organs. In particular, follicle stimulating hormones (FSH) and luteinizing hormone (LH) are released by the anterior pituitary gland. These hormones, in combination, regulate the functioning of the gonads to produce testosterone in the testis and progesterone and estrogen in the ovaries, as well as regulating the production and maturation of gametes. These hormones are sometimes referred to as gonadotropins or gonadotropic hormones. The release of a hormone by the anterior lobe of the pituitary gland usually requires a prior release of another class of hormones produced by the hypothalamus. One of the hypothalamic hormones acts as a factor that triggers the release of the gonadotropic hormones, namely, LH and FSH, and has been designated luteinizing hormone releasing factor (LRF) or LH-RH or GnRH.
It has long been felt that a mechanism may operate whereby hormones produced by the gonads would, by a feedback loop, regulate the secretion of gonadotropins by the pituitary gland. Such a mechanism was originally proposed by D. R. McCullagh in 1932, (Science 76, 19-20). A hypothetical gonadal substance, designated inhibin, which was non-steroidal but proteinaceous in nature was proposed to be released into general circulation and to act specifically on the pituitary gland, selectively inhibiting the secretion of FSH, but not of LH. In recent years, inhibin-like activity, i.e., the selective inhibition of FSH, has been reported in extracts of testis, spermatozoa, rete testis fluid, seminal plasma and ovarian follicular fluid. Other researchers have reported inhibition of the secretion of both LH and FSH by rete testis fluid, seminal plasma, Sertoli cell culture fluid, granulosa cell culture fluid, and follicular fluid. The selective inhibition of LH and FSH release from the LRF-stimulated pituitary by a substance of gonadal origin will be referred to herein as gonadostatin activity, and the gonadal substance which selectively inhibits the stimulated LH and FSH secretion from the pituitary will be referred to as gonadostatin. Although several investigators have observed inhibin and/or gonadostatin activity in crude or partially purified gonadal extracts, none has heretofore isolated and characterized a substance which is responsible for these activities.